18 results on '"Shahed Hussain"'
Search Results
2. Anxiety, Depression, and Pain: Considerations in the Treatment of Patients with Uncontrolled Hypertension
- Author
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Mohamed Serhan Hamam, Elizabeth Kunjummen, Stephanie Bennett, Shahed Hussain, Joseph B Miller Md, and Mohamed Nasereldin
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Nephrology ,medicine.medical_specialty ,Anxiety depression ,Anxiety ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Internal Medicine ,medicine ,Humans ,030212 general & internal medicine ,Intensive care medicine ,Depression (differential diagnoses) ,Depression ,business.industry ,Chronic pain ,medicine.disease ,Anxiety Disorders ,Mental health ,Treatment efficacy ,Hypertension ,Chronic Pain ,medicine.symptom ,business - Abstract
The association between mental health, pain, and treatment-resistant hypertension is an important consideration for treating physicians. We review and discuss the connection between conditions of anxiety, depression, and chronic pain and their effect on uncontrolled hypertension. There is significant co-occurrence of hypertension with anxiety, depression, and chronic pain which may lead to undertreatment of hypertension and undertreatment of the underlying mental health disorder. The association between mental health and hypertension is complex and is modulated by physiologic and environmental factors. Physicians treating patients with hypertension should be cognizant of the role anxiety, depression, and chronic pain play in treatment efficacy and compliance. Patients undergoing treatment should be screened for mental health disorders at treatment initiation and frequently thereafter to ensure optimal overall health and compliance.
- Published
- 2020
3. One-Pot Biocatalytic Cascade Reduction of Cyclic Enimines for the Preparation of Diastereomerically Enriched N-Heterocycles
- Author
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Thomas W. Thorpe, Scott P. France, Shahed Hussain, James R. Marshall, Wojciech Zawodny, Juan Mangas-Sanchez, Sarah L. Montgomery, Roger M. Howard, David S. B. Daniels, Rajesh Kumar, Fabio Parmeggiani, and Nicholas J. Turner
- Subjects
Imine ,General Chemistry ,Reductase ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Combinatorial chemistry ,Catalysis ,0104 chemical sciences ,Reduction (complexity) ,Hydrolysis ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,chemistry ,Amine gas treating ,hormones, hormone substitutes, and hormone antagonists - Abstract
Ene-reductases (EREDs) catalyze the reduction of electron-deficient C═C bonds. Herein, we report the first example of ERED-catalyzed net reduction of C═C bonds of enimines (α,β-unsaturated imines). Preliminary studies suggest their hydrolyzed ring-open ω-amino enones are the likely substrates for this step. When combined with imine reductase (IRED)-mediated C═N reduction, the result is an efficient telescoped sequence for the preparation of diastereomerically enriched 2-substituted saturated amine heterocycles.
- Published
- 2019
4. One-Pot Biocatalytic Cascade Reduction of Cyclic Enimines for the Preparation of Diastereomerically Enriched
- Author
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Thomas W, Thorpe, Scott P, France, Shahed, Hussain, James R, Marshall, Wojciech, Zawodny, Juan, Mangas-Sanchez, Sarah L, Montgomery, Roger M, Howard, David S B, Daniels, Rajesh, Kumar, Fabio, Parmeggiani, and Nicholas J, Turner
- Subjects
Molecular Structure ,Heterocyclic Compounds ,Biocatalysis ,Stereoisomerism ,Imines ,Oxidoreductases ,Oxidation-Reduction - Abstract
Ene-reductases (EREDs) catalyze the reduction of electron-deficient C═C bonds. Herein, we report the first example of ERED-catalyzed net reduction of C═C bonds of enimines (α,β-unsaturated imines). Preliminary studies suggest their hydrolyzed ring-open ω-amino enones are the likely substrates for this step. When combined with imine reductase (IRED)-mediated C═N reduction, the result is an efficient telescoped sequence for the preparation of diastereomerically enriched 2-substituted saturated amine heterocycles.
- Published
- 2019
5. Synergistic Chemo/Biocatalytic Synthesis of Alkaloidal Tetrahydroquinolines
- Author
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Stephen P. Marsden, Nicholas J. Turner, Shahed Hussain, and Sebastian C. Cosgrove
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chemistry.chemical_classification ,Amine oxidase ,010405 organic chemistry ,Cyclohexylamine oxidase ,Enantioselective synthesis ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,Catalysis ,0104 chemical sciences ,Enzyme ,chemistry ,Biocatalysis ,Alkyl - Abstract
The power of complementary chemocatalytic and biocatalytic transformations is demonstrated in the asymmetric synthesis of 2-substituted tetrahydroquinolines. A series of racemic tetrahydroquinolines were synthesized through a convergent one-pot Rh(I)-catalyzed addition/condensation sequence of alkyl vinyl ketones and aminophenylboronic acids. The resulting tetrahydroquinolines were thereafter shown to be substrates for the flavin-dependent enzyme cyclohexylamine oxidase, and preparative-scale deracemizations have been demonstrated on these high-value targets.
- Published
- 2018
6. Stereoselectivity and Structural Characterization of an Imine Reductase (IRED) from Amycolatopsis orientalis
- Author
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Godwin A. Aleku, Henry Man, Scott P. France, Friedemann Leipold, Shahed Hussain, Laura Toca-Gonzalez, Rebecca Marchington, Sam Hart, Johan P. Turkenburg, Gideon Grogan, and Nicholas J. Turner
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chemistry.chemical_classification ,biology ,010405 organic chemistry ,Chemistry ,Stereochemistry ,Imine ,Iminium ,Active site ,General Chemistry ,Reductase ,010402 general chemistry ,biology.organism_classification ,01 natural sciences ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,Biocatalysis ,Oxidoreductase ,biology.protein ,Stereoselectivity ,Amycolatopsis orientalis - Abstract
The imine reductase AoIRED from Amycolatopsis orientalis (Uniprot R4SNK4) catalyzes the NADPH-dependent reduction of a wide range of prochiral imines and iminium ions, predominantly with (S)-selectivity and with e.e.s of up to >99%. AoIRED displays up to 100-fold greater catalytic efficiency for 2-methyl-1-pyrroline (2MPN) compared to other IREDs, such as the enzyme from Streptomyces sp. GF3546, which also exhibits (S)-selectivity, and thus AoIRED is an interesting candidate for preparative synthesis. AoIRED exhibits unusual catalytic properties, with inversion of stereoselectivity observed between structurally similar substrates, and also, in the case of 1-methyl-3,4-dihydroisoquinoline, for the same substrate, dependent on the age of the enzyme after purification. The structure of AoIRED has been determined in an ‘open’ apo-form, revealing a canonical dimeric IRED fold in which the active site is formed between the N- and C-terminal domains of participating monomers. Co-crystallisation with NADPH gave a ‘closed’ form in complex with the cofactor, in which a relative closure of domains, and associated loop movements, has resulted in a much smaller active site. A ternary complex was also obtained by co-crystallization with NADPH and 1-methyl-1,2,3,4-tetrahydroisoquinoline [(MTQ], and reveals a binding site for the (R)-amine product which places the chiral carbon within 4 Å of the putative location of the C4 atom of NADPH that delivers hydride to the C=N bond of the substrate. The ternary complex has permitted structure-informed mutation of the active site, resulting in mutants including Y179A, Y179F and N241A, of altered activity and stereoselectivity.
- Published
- 2016
7. One-Pot Cascade Synthesis of Mono- and Disubstituted Piperidines and Pyrrolidines using Carboxylic Acid Reductase (CAR), ω-Transaminase (ω-TA), and Imine Reductase (IRED) Biocatalysts
- Author
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Scott P. France, Shahed Hussain, Andrew M. Hill, Lorna J. Hepworth, Roger M. Howard, Keith R. Mulholland, Sabine L. Flitsch, and Nicholas J. Turner
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010405 organic chemistry ,Stereochemistry ,Imine ,Substituent ,General Chemistry ,Reductase ,010402 general chemistry ,01 natural sciences ,Catalysis ,Pyrrolidine ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Biocatalysis ,Stereoselectivity ,Piperidine ,Methyl group - Abstract
Access to enantiomerically pure chiral mono- and disubstituted piperidines and pyrrolidines has been achieved using a biocatalytic cascade involving carboxylic acid reductase (CAR), ω-transaminase (ω-TA), and imine reductase (IRED) enzymes. Starting from keto acids or keto aldehydes, substituted piperidine or pyrrolidine frameworks can be generated in high conversion, ee, and de in one pot, with each biocatalyst exhibiting chemo-, regio-, and/or stereoselectivity during catalysis. The study also includes a systematic investigation of the effect of the position of a methyl group ring substituent on the IRED-catalyzed reduction of a chiral imine. Analysis of the selectivity observed in these reactions revealed an interesting balance between substrate versus enzyme control; the configurations of the products obtained were rationalized on the basis of minimizing 1,3- or 1,2-steric interactions with incoming NADPH.
- Published
- 2016
8. Combined Imine Reductase and Amine Oxidase Catalyzed Deracemization of Nitrogen Heterocycles
- Author
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Marta Pontini, Rachel S. Heath, Shahed Hussain, and Nicholas J. Turner
- Subjects
Amine oxidase ,Oxidase test ,010405 organic chemistry ,Monoamine oxidase ,Organic Chemistry ,Imine ,Ammonia borane ,Reductase ,010402 general chemistry ,01 natural sciences ,Catalysis ,0104 chemical sciences ,Enzyme catalysis ,Inorganic Chemistry ,chemistry.chemical_compound ,chemistry ,Organic chemistry ,Physical and Theoretical Chemistry ,Enantiomeric excess - Abstract
A novel amine oxidase (AO)/imine reductase (IRED) system was developed for the deracemization of racemic amines. By combining (R)-6-hydroxy-d-nicotine oxidase (6-HDNO) with an (R)-IRED, a panel of racemic 2-substituted piperidines and pyrrolidines were deracemized to yield the (S)-amines in high yields and enantiomeric excess values. Other N-heterocycles were deracemized with monoamine oxidase (MAO-N) or 6-HDNO in combination with ammonia borane, which allowed comparison of the two enzyme deracemization approaches with that involving a chemical reducing agent.
- Published
- 2015
9. Simple and versatile laboratory scale CSTR for multiphasic continuous-flow chemistry and long residence times
- Author
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Ibrahim E. Salama, Bao N. Nguyen, Shahed Hussain, Mary E. Bayana, Adam D. Clayton, Michael R. Chapman, A. John Blacker, Maria H. T. Kwan, Katherine E. Jolley, Carlos González Niño, Lisa A. Thompson, Nikil Kapur, Georgina E. King, Mariam Hussain, and Nicholas J. Turner
- Subjects
010405 organic chemistry ,Continuous flow ,business.industry ,Chemistry ,Organic Chemistry ,Mixing (process engineering) ,Continuous stirred-tank reactor ,Laboratory scale ,010402 general chemistry ,ResearchInstitutes_Networks_Beacons/manchester_institute_of_biotechnology ,01 natural sciences ,0104 chemical sciences ,Chemical engineering ,Cascade ,Manchester Institute of Biotechnology ,Physical and Theoretical Chemistry ,Reactor geometry ,Process engineering ,business - Abstract
A universal multi-stage cascade CSTR has been developed which is suitable for a wide range of continuous-flow processes. Coined by our group the ‘Freactor’ (free-to-access reactor), the new reactor integrates the efficiency of pipe-flow processing with the advanced mixing of a CSTR, delivering a general ‘plug-and-play’ reactor platform which is well-suited to multiphasic continuous-flow chemistry. Importantly, the reactor geometry is easily customized to accommodate reactions requiring long residence times (≥ 3 hours tested).
- Published
- 2017
10. A reductive aminase from Aspergillus oryzae
- Author
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Godwin A. Aleku, Scott P. France, Henry Man, Juan Mangas-Sanchez, Sarah L. Montgomery, Mahima Sharma, Friedemann Leipold, Shahed Hussain, Gideon Grogan, and Nicholas J. Turner
- Subjects
Models, Molecular ,Aspergillus oryzae ,General Chemical Engineering ,Imine ,010402 general chemistry ,01 natural sciences ,Reductive amination ,chemistry.chemical_compound ,Aminohydrolases ,Oxidoreductase ,Organic chemistry ,Amines ,Enantiomeric excess ,Amination ,chemistry.chemical_classification ,Molecular Structure ,biology ,010405 organic chemistry ,Chemistry ,General Chemistry ,biology.organism_classification ,Combinatorial chemistry ,0104 chemical sciences ,Biocatalysis ,Mutation ,Amine gas treating ,Oxidation-Reduction - Abstract
Reductive amination is one of the most important methods for the synthesis of chiral amines. Here we report the discovery of an NADP(H)-dependent reductive aminase from Aspergillus oryzae (AspRedAm, Uniprot code Q2TW47) that can catalyse the reductive coupling of a broad set of carbonyl compounds with a variety of primary and secondary amines with up to >98% conversion and with up to >98% enantiomeric excess. In cases where both carbonyl and amine show high reactivity, it is possible to employ a 1:1 ratio of the substrates, forming amine products with up to 94% conversion. Steady-state kinetic studies establish that the enzyme is capable of catalysing imine formation as well as reduction. Crystal structures of AspRedAm in complex with NADP(H) and also with both NADP(H) and the pharmaceutical ingredient (R)-rasagiline are reported. We also demonstrate preparative scale reductive aminations with wild-type and Q240A variant biocatalysts displaying total turnover numbers of up to 32,000 and space time yields up to 3.73 g l−1 d−1. An enzyme (AspRedAm) capable of coupling carbonyls with a variety of amines in a reductive amination has now been discovered. Kinetic studies revealed that the enzyme catalysed both the imine formation step, as well as the reduction step. Structure and mutagenesis studies have highlighted essential catalytic residues and preparative scale examples have demonstrated total turnover numbers of up to 32,000.
- Published
- 2017
11. De Novo Enzyme Cascades in Whole Cells for the Synthesis of Chiral Cyclic Amines
- Author
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Lorna J. Hepworth, Scott P. France, Shahed Hussain, Peter Both, Nicholas J. Turner, and Sabine L. Flitsch
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chemistry.chemical_classification ,010405 organic chemistry ,Transamination ,Stereochemistry ,Carboxylic acid ,Imine ,Enantioselective synthesis ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Biocatalysis ,Amine gas treating ,Enantiomeric excess - Abstract
The increasing diversity of reactions mediated by biocatalysts has led to development of multistep in vitro enzyme cascades, taking advantage of generally compatible reaction conditions. The construction of pathways within single whole cell systems is much less explored, yet has many advantages. Herein we report the generation of a successful whole cell de novo enzyme cascade for the diastereoselective and/or enantioselective conversion of simple, linear keto acids into valuable cyclic amine products. The pathway starts with carboxylic acid reduction that triggers a transamination, imine formation, and subsequent imine reduction. Construction and optimization of the system was achieved by standard genetic manipulation and the cascade required only starting material, amine donor, and whole cell catalyst with cofactors provided internally by glucose metabolism. A panel of synthetic keto acids provided access to piperidines in high conversions (up to 93%) and enantiomeric excess (up to 93%).
- Published
- 2017
12. Asymmetric Reduction of Cyclic Imines Catalyzed by a Whole-Cell Biocatalyst Containing an (S)-Imine Reductase
- Author
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Nicholas J. Turner, Diego Ghislieri, Friedemann Leipold, and Shahed Hussain
- Subjects
biology ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Imine ,Enantioselective synthesis ,Reductase ,010402 general chemistry ,biology.organism_classification ,01 natural sciences ,Streptomyces ,Catalysis ,0104 chemical sciences ,Inorganic Chemistry ,Reduction (complexity) ,chemistry.chemical_compound ,Biocatalysis ,Organic chemistry ,Physical and Theoretical Chemistry ,Whole cell - Published
- 2013
13. Signal reshaping using dominant harmonic for pitch estimation of noisy speech
- Author
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Shahed Hussain, Md. N. Ibne Nazrul, M. T. Hossain Setu, and Md. Kamrul Hasan
- Subjects
Engineering ,business.industry ,Speech recognition ,Autocorrelation ,Audio time-scale/pitch modification ,Fine pitch ,Pitch detection algorithm ,Test method ,Signal ,Computer Science::Sound ,Control and Systems Engineering ,Signal Processing ,Harmonic ,Reference database ,Computer Vision and Pattern Recognition ,Electrical and Electronic Engineering ,business ,Software - Abstract
A simple yet powerful method for pitch estimation of noisy speech is presented in this paper. The basic idea is to use the rectified dominant harmonic for signal reshaping. The main advantage of using the reshaped signal is the enhanced pitch peak as compared to other non-pitch peaks. The normalized autocorrelation function of the processed speech is used for pitch extraction. The performance of the proposed method is tested and compared with those of recent methods using the Keele pitch extraction reference database. Comparative results show that the proposed method can detect pitch with better accuracy in terms of gross and fine pitch errors as compared to other reported techniques.
- Published
- 2006
14. Structure, Activity and Stereoselectivity of NADPH-Dependent Oxidoreductases Catalysing the S-Selective Reduction of the Imine Substrate 2-Methylpyrroline
- Author
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Nicholas J. Turner, Elizabeth Wells, Johan P. Turkenburg, Henry Man, Sam Hart, Gideon Grogan, Shahed Hussain, and Friedemann Leipold
- Subjects
Models, Molecular ,Pyrrolidines ,Stereochemistry ,Imine ,Gram-Positive Bacteria ,Biochemistry ,Substrate Specificity ,Residue (chemistry) ,chemistry.chemical_compound ,Oxidoreductase ,Catalytic Domain ,NADH, NADPH Oxidoreductases ,Tyrosine ,Molecular Biology ,chemistry.chemical_classification ,biology ,Sequence Homology, Amino Acid ,Organic Chemistry ,Active site ,Enzyme ,chemistry ,biology.protein ,Biocatalysis ,Molecular Medicine ,Stereoselectivity ,Imines ,Selectivity ,Oxidation-Reduction - Abstract
Oxidoreductases from Streptomyces sp. GF3546 [3546-IRED], Bacillus cereus BAG3X2 (BcIRED) and Nocardiopsis halophila (NhIRED) each reduce prochiral 2-methylpyrroline (2MPN) to (S)-2-methylpyrrolidine with >95 % ee and also a number of other imine substrates with good selectivity. Structures of BcIRED and NhIRED have helped to identify conserved active site residues within this subgroup of imine reductases that have S selectivity towards 2MPN, including a tyrosine residue that has a possible role in catalysis and superimposes with an aspartate in related enzymes that display R selectivity towards the same substrate. Mutation of this tyrosine residue-Tyr169-in 3546-IRED to Phe resulted in a mutant of negligible activity. The data together provide structural evidence for the location and significance of the Tyr residue in this group of imine reductases, and permit a comparison of the active sites of enzymes that reduce 2MPN with either R or S selectivity.
- Published
- 2014
15. An (
- Author
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Shahed, Hussain, Friedemann, Leipold, Henry, Man, Elizabeth, Wells, Scott P, France, Keith R, Mulholland, Gideon, Grogan, and Nicholas J, Turner
- Subjects
biocatalysis ,Communication ,amines ,asymmetric catalysis ,reduction ,nitrogen heterocycles ,Communications - Abstract
Although the range of biocatalysts available for the synthesis of enantiomerically pure chiral amines continues to expand, few existing methods provide access to secondary amines. To address this shortcoming, we have over‐expressed the gene for an (R)‐imine reductase [(R)‐IRED] from Streptomyces sp. GF3587 in Escherichia coli to create a recombinant whole‐cell biocatalyst for the asymmetric reduction of prochiral imines. The (R)‐IRED was screened against a panel of cyclic imines and two iminium ions and was shown to possess high catalytic activity and enantioselectivity. Preparative‐scale synthesis of the alkaloid (R)‐coniine (90 % yield; 99 % ee) from the imine precursor was performed on a gram‐scale. A homology model of the enzyme active site, based on the structure of a closely related (R)‐IRED from Streptomyces kanamyceticus, was constructed and used to identify potential amino acids as targets for mutagenesis.
- Published
- 2014
16. ChemInform Abstract: Asymmetric Reduction of Cyclic Imines Catalyzed by a Whole-Cell Biocatalyst Containing an (S)-Imine Reductase
- Author
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Shahed Hussain, Diego Ghislieri, Nicholas J. Turner, and Friedemann Leipold
- Subjects
Reduction (complexity) ,chemistry.chemical_compound ,Biocatalysis ,Chemistry ,Imine ,General Medicine ,Reductase ,Whole cell ,Combinatorial chemistry ,Pyrrole derivatives ,Catalysis - Published
- 2014
17. Unconditionally stable alternate-direction-explicit 2D FDTD algorithm
- Author
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Shahed Hussain and Hideki Asai
- Subjects
Electromagnetic field ,Fdtd algorithm ,Courant–Friedrichs–Lewy condition ,Mathematical analysis ,Finite-difference time-domain method ,Finite difference method ,Applied mathematics ,Probability density function ,Limit (mathematics) ,Inverse problem ,Mathematics - Abstract
This paper proposes a new technique (explicit technique, yet unconditionally stable) for 2D FDTD algorithm. This method is not limited by the Courant-Friedrich-Levy (CFL) condition and is unconditionally stable beyond the CFL limit; though this is an explicit method. Here numerical formulations are presented and simulation results are compared with other FDTD algorithms.
- Published
- 2009
18. Substrate promiscuity of cytochrome P450 RhF
- Author
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Nicholas J. Turner, Sabine L. Flitsch, Shahed Hussain, Paul P. Kelly, Dominique Richardson, Elaine O'Reilly, and Mark Corbett
- Subjects
chemistry.chemical_classification ,biology ,010405 organic chemistry ,Stereochemistry ,Cytochrome P450 ,Substrate (chemistry) ,010402 general chemistry ,Directed evolution ,01 natural sciences ,Catalysis ,0104 chemical sciences ,Enzyme ,chemistry ,biology.protein - Abstract
Cytochrome P450 RhF displays a high degree of substrate promiscuity, mediating a range of O-dealkylations, aromatic hydroxylations, epoxidations and asymmetric sulfoxidations. The self-sufficient nature of this CYP coupled with its ability to catalyse the oxidation of a wide range of functional groups highlights this enzyme as an excellent starting template for directed evolution and promising alternate to P450 BM3.
- Published
- 2013
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